Age and its Impact on Outcomes with Intraabdominal Infections Drew Farmer, Jeffrey M. Tessier, James M. Sanders, Robert G. Sawyer, Billy J. Moore, Therese M. Duane Baylor University Medical Center; Dallas, TX JPS Health Network; Fort Worth, TX Departments of Surgery and Public Health Sciences, University of Virginia; Charlottesville, VA

Introduction Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial Prospective, multicenter, randomized controlled trial Source control with short vs. longer abx therapy No difference in outcomes Age plays a significant role in the etiology of cIAIs Correlation between age and outcomes after therapy was not investigated

Purpose To determine if patients 65 years and older with complicated intraabdominal infection have different outcomes compared with their younger counterparts when treated with similar regimens

Methods Post-hoc analysis of the STOP-IT trial database Patients were stratified by age <65 or ≥65 years of age. Characteristics of the groups were analyzed including clinical indicators of disease severity infection acquisition location site of the infection

Methods Subgroup analyses with focus on sites of infection source control procedures antimicrobial therapy Primary outcomes: surgical site infection (SSI) recurrent intraabdominal infection (recIAI) Death composite of all three Multivariate analysis was performed to identify independent predictors of outcomes

Results Table 1. Baseline characteristics stratified by age Age < 65 Years (N=398) Age ≥ 65 Years (N=120) P-valueb Gender, no. (%)   Male 217 (54.5) 72 (60.0) 0.30 Race, no. (%) 0.06 White 301 (75.6) 103 (85.8) Black 80 (20.1) 14 (11.7) Othera 17 (4.3) 3 (2.5) Hispanic, no. (%) 29 (7.3) 6 (5.0) 0.38 Body Mass Index, mean±SD 29.4 ± 9.3 27.7 ± 7.0 0.03 APACHE II score, mean±SD 9.0 ± 5.8 13.4 ± 5.4 <0.0001

Results

Results Table 2. Infection characteristics and treatment strategies stratified by age, N=518  Characteristic Age < 65 (N=398) Age ≥ 65 (N=120) P-value Maximum white blood cell count, per mm3, mean±SD 16.7 ± 10.1 15.3 ± 7.5 0.09 Maximum body temperature, 0C, mean±SD 37.8 ± 0.9 37.5 ± 0.8 0.002   Setting of acquisition of cIAI, no. (%) 0.19 Community-acquired 240 (60.5) 81 (67.5) Healthcare-associated 105 (26.5) 22 (18.3) Hospital-acquired 52 (13.1) 17 (14.2) Total antibiotic days, mean±SD 7.4 ± 5.7 7.5 ± 4.9 0.95

Results

Results

Results Site of Infection Source-control Procedure Colon or Rectum   Source-control Procedure Site of Infection Colon or Rectum N=177 Small Intestine N= 73 Appendix Biliary Tree N= 56 < 65 N= 119 > 65 N= 58 P-Valuea N= 65 N= 8 P-Value1 N= 68 N= 5 N= 36 N= 20 Percutaneous drainage, no. (%) 38 (31.9) 12 (20.7) 0.15 20 (30.8) 3 (37.5) 0.70 26 (38.2) (0.0) 10 (27.8) 7 (35.0) 0.76 Resection and anastomosis or closure, no. (%) 29 (24.4) 18 (31.0) 0.37 17 (26.2) 2 (25.0) 1.00 19 (27.9) 1 (20.0) 12 (33.3) 6 (30.0) Surgical drainage only, 28 (23.5) (20.7) 0.71 (18.5) 0.64 14 (20.6) (40.0) 0.30 9 4 0.75 Resection and proximal diversion, (14.3) 11 (19.0) 0.51 (16.9) (12.5) (8.8) 0.09 (5.6) 0.53 Simple closure, no. (%) (3.4) 5 (8.6) 0.16 (6.2) (2.9) (10.0) 0.61 Surgical drainage and diversion, no. (%) 3 (2.5) 0.55 (1.5) (1.47) (2.8) (5.0) Results

Results Site of Infection Antimicrobial Colon or Rectum N=177   Antimicrobial Site of Infection Colon or Rectum N=177 Small Intestine N= 73 Appendix Biliary Tree N= 56 < 65 N= 119 > 65 N= 58 P-Valuea N= 65 N= 8 N= 68 N= 5 N= 36 N= 20 P- Valuea Amoxcillin or Amoxicillin-clavulanate, no. (%) 6 (5.0) 2 (3.5) 1.00 4 (6.2) 1 (12.5) 0.45 9 (13.2) (0.0) (16.7) 5 (25.0) 0.50 Piperacillin-tazobactam, 61 (51.3) 36 (62.1) 0.27 30 (46.2) (50.0) 21 (30.9) (80.0) 0.04 28 (77.8) 13 (65.0) 0.35 Ertapenem, 17 (14.3) (1.7) 0.01 7 (10.8) (25) 0.25 11 (16.2) (20.0) (2.8) Meropenem/ imipenem-cilastatin, 3 (5.2) (1.5) (8.3) Ceftriaxone, 0.18 0.36 Cephamycinb, (7.6) 0.17 (7.7) 0.51 (10.3) 0.55 Fluoroquinolonec, no. (%) 37 (31.1) 19 (32.8) 0.86 18 (27.7) 0.67 23 (33.8) (40.0) 10 (27.8) Metronidazole, 39 (31.0) 0.87 (32.3) 0.42 32 (47.1) 8 0.10 Vancomycin, 35 (29.4) 12 (18.5) (37.5) (8.8) (22.2) (30.0) 0.54 Results

Results Of the primary outcomes only death was significantly different between the age groups More prevalent in the ≥ 65 years group (3.3% vs. 0.3%, p=0.01) No difference was seen in rates of Surgical site infection (7.3% vs. 9.2%, p=0.50) Recurrent intraabdominal infection (14.4% vs. 15.8%, p=0.69) Composite outcome (20.4% vs. 26.7%, p=0.14) Multivariate analyses did not reveal age as an independent predictor of the composite or individual outcomes

Discussion Important to understand pathophysiology of intraabdominal infection in the elderly Over 23% of the patients in the recently published STOP-IT trial were sixty-five years of age Advanced age has previously been shown to be an independent risk factor for mortality in the patient with an IAI SIS and IDSA guidelines list advanced age as a factor for predicting failure of source control Recommend escalated antimicrobial therapy for empiric treatment of community acquired infections in this population Vulnerable to the virulent effects of certain pathogens increasing their mortality rate

Discussion Current recommendations suggesting a more aggressive approach to the treatment of the elderly make the findings in this study provocative No statistical differences in prevalence of surgical site infections and recurrent intraabdominal infections between age groups Groups had same duration of antimicrobial therapy and type of source control Although more colorectal sources in ≥ 65 vs. more appendix and SB in < 65 the source control procedures were similar Questionable whether there is need for a more aggressive approach as recommended by the SIS and IDSA

Discussion These findings suggest that adherence to these guidelines was inconsistent, yet infection-specific differences in outcomes between the two groups were not statistically significant.

Limitations Post hoc analysis of prospectively collected data Smaller sample size especially with subgroup analysis Risk of Type II error

Conclusions Despite distinct differences in etiology, this study confirms that a similar approach is important such that all patients should be expeditiously treated with source control and antibiotics. Similar duration of therapy can be applied to the elderly population Guidelines that recommend a different approach to patients with advanced age deserve further evaluation